Research Interests:

My research interests involve understanding at the molecular level how transcription is regulated in the Notch signaling pathway. The Notch pathway is a highly conserved cell-to-cell signaling mechanism in metazoans that is essential for embryonic development and tissue homeostasis. Aberrant Notch signaling underlies the pathogenesis of many human diseases, including congenital defects, cardiovascular disease, and cancer. Notch signaling ultimately results in changes in gene expression, which is regulated by CSL. CSL is a DNA-binding transcription factor that interacts with corepressors and coactivators to regulate transcriptional repression and activation, respectively, of Notch target genes.

My laboratory uses x-ray crystallography to determine the structures of CSL-coregulator complexes, and other biophysical techniques, such as isothermal titration calorimetry (ITC), to characterize the binding and affinity of these complexes. In parallel with these studies, we use cellular and biochemical methods to characterize and functionally validate our structural models. Ultimately, the goal of this research is to provide a molecular explanation for how transcription is regulated in the Notch pathway, which is critical for understanding Notch signaling in normal biological contexts and in diseased states such as cancer.

Kovall, R. A., & Matthews, B. W.
(1998).
Structural, functional, and evolutionary relationships between lambda-exonuclease and the type II restriction endonucleases.
. Proceedings of the National Academy of Sciences of the United States of America
, 95
(14)
, 7893-7.